Abstract 641TiP
Background
Treatment options are limited for pts with mCRPC that progresses with NHAs or docetaxel, and outcomes are poor for the ∼20% of pts who develop t-NE. Pembro showed antitumor activity as monotherapy in docetaxel-pretreated pts with adenocarcinoma mCRPC in the phase II KEYNOTE-199 trial and in combination with olaparib in cohort A of the phase III KEYNOTE-365 trial. The TIGIT inhibitor vibostolimab showed antitumor activity in preclinical tumor models. Combining PD-1 and TIGIT inhibition might have enhanced benefit in adenocarcinoma mCRPC and t-NE versus monotherapy.
Trial design
KEYNOTE-365 is a nonrandomized, open-label, multicohort, phase Ib/II study (NCT02861573) to evaluate different pembro combination therapies in several populations of pts with mCRPC. Pts enrolled in cohort G must have adenocarcinoma of the prostate without small cell histology per investigator. Pts enrolled in cohort H must have t-NE (≥1% neuroendocrine cells in a recent biopsy specimen confirmed by central histology review). Each cohort of 40-100 pts includes adults with ECOG PS 0/1 who previously received docetaxel for mCRPC. Prior treatment with ≤2 NHAs (hormone-sensitive metastatic prostate cancer or mCRPC) and 1 other chemotherapy for mCRPC were permitted. Pts enrolled in cohort H must have had progressive t-NE within <6 months of starting an NHA and <6 cycles of docetaxel. Both cohorts will receive MK-7684A, a coformulation of pembro 200 mg and vibostolimab 200 mg, IV Q3W. Treatment will continue until disease progression, withdrawal of consent, or other discontinuation event. AEs will be monitored throughout the trial up to 30 days after discontinuation (90 days for serious AEs) and graded using CTCAE v4.0. CT/MRI will be performed at screening, Q9W through week 54, and Q12W thereafter. Primary end points are safety and tolerability, PSA response rate, and ORR per RECIST v1.1 by blinded independent central review (BICR). Secondary end points are time to PSA progression, ORR, and rPFS per PCWG3-modified RECIST v1.1 by BICR; DOR and DCR per RECIST v1.1 and PCWG3-modified RECIST v1.1 by BICR; and OS.
Clinical trial identification
NCT02861573, August 10, 2016.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
J.S. de Bono: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Bioxcel Therapeutics; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Cellcentric; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Genentech Roche; Financial Interests, Personal, Advisory Board: Genmab; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Harpoon; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Menarini Silicon Biosystems; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Orion Pharma; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Qiagen; Financial Interests, Personal, Advisory Board: Sanofi Aventis; Financial Interests, Personal, Advisory Board: Sierra Oncology; Financial Interests, Personal, Advisory Board: Taiho; Financial Interests, Personal, Advisory Board: Terumo; Financial Interests, Personal, Advisory Board: Vertex Pharmaceuticals; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Cellcentric; Financial Interests, Institutional, Research Grant: Daiichi; Financial Interests, Institutional, Research Grant: Genentech Roche; Financial Interests, Institutional, Research Grant: Genmab; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Harpoon; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Merck Serono; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: Orion Pharma; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Sanofi Aventis; Financial Interests, Institutional, Research Grant: Sierra Oncology; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Vertex Pharmaceuticals. N.D. Shore: Financial Interests, Personal, Advisory Role: Abbvie, Amgen, Astellas, AstraZeneca, Aurora Oncology, Bayer, BMS, Boston Scientific, Clovis Oncology, Cold Genesys, Dendreon, Exact Imaging, Exact Sciences, FerGene, Foundation Medicine, GenesisCare, Invitae, Janssen, MDxhealth, Merck, Myovant, Myriad, N; Financial Interests, Personal, Speaker’s Bureau, Expert Testimony: Aurora Oncology, Bayer, Clovis Oncology, Foundation Medicine, Guardant, Janssen, Merck, Myovant, Pfizer, Tolmar. G. Kramer: Financial Interests, Personal, Advisory Role: Astellas, AstraZeneca, Bayer, BMS, psen, Janssen, MSD, Novartis, Sanofi Genzyme, Takeda, Amgen; Financial Interests, Institutional, Research Grant: Bayer. A.M. Joshua: Financial Interests, Institutional, Other, Honoraria: Merck. X.T. Li: Financial Interests, Personal and Institutional, Full or part-time Employment: MSD China. C.H. Poehlein: Financial Interests, Personal and Institutional, Full or part-time Employment: Merck; Financial Interests, Personal and Institutional, Leadership Role: Merck; Financial Interests, Personal and Institutional, Stocks/Shares: Merck. C. Schloss: Financial Interests, Personal and Institutional, Full or part-time Employment: Merck; Financial Interests, Personal and Institutional, Stocks/Shares: Merck. E.Y. Yu: Financial Interests, Personal, Advisory Role: Janssen, Bayer, Merck, Seattle Genetics, Clovis Oncology, Advanced Accelerator Applications, Sanofi, Abbvie, Myovant Sciences; Financial Interests, Institutional, Research Grant: Dendreon, Merck, Seattle Genetics, Daiichi Sankyo, Taiho Pharmaceutical, Pharmacyclics, Blue Earth Diagnostics, Bayer.